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Natural product

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Title: Natural product  
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Subject: Paclitaxel, Steroid, Elias James Corey, Atta ur Rahman (scientist), Cerberin
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Natural product

Paclitaxel (Taxol) is a natural product derived from the yew tree.[1]

A natural product is a

 This article incorporates text from the public domain 1913 Webster's Dictionary.

  • Natural Products page, William Reusch (2010) Virtual Textbook of Organic Chemistry, Ann Arbor, Mich.:Michigan State University, Department of Chemistry
  • NAPROC-13, Base de datos de Carbono 13 de Productos Naturales y Relacionados (Carbon-13 Database of Natural Products and Related Substances), Spanish language tools to facilitate structural identification of natural products

External links


  • Hanson JR (2003). Natural Products: The Secondary Metabolites. Royal Society of Chemistry.  
  • Liang X-T, Fang W-S, ed. (2006). Medicinal Chemistry of Bioactive Natural Products. Wiley-Interscience.  
  • Peter B, Kaufman PB (1999). Natural Products from Plants. CRC Press.  
  • Bhat SV, Nagasampagi BA, Sivakumar M (2005). Chemistry of Natural Products (2 ed.). Berlin: Springer.  

Further reading

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  2. ^ Webster's Revised Unabridged Dictionary (1913). "Natural product". Free Online Dictionary and C. & G. Merriam Co. A chemical substance produced by a living organism; - a term used commonly in reference to chemical substances found in nature that have distinctive pharmacological effects. Such a substance is considered a natural product even if it can be prepared by total synthesis. 
  3. ^ "All natural". Nature Chemical Biology 3 (7): 351. 2007.  
  4. ^ a b Samuelson G (1999). Drugs of Natural Origin: A Textbook of Pharmacognosy. Taylor & Francis Ltd,.  
  5. ^ National Center for Complementary and Integrative Health (2013-07-13). "Natural Products Research—Information for Researchers | NCCIH". U.S. Department of Health & Human Services. Natural products include a large and diverse group of substances from a variety of sources. They are produced by marine organisms, bacteria, fungi, and plants. The term encompasses complex extracts from these producers, but also the isolated compounds derived from those extracts. It also includes vitamins, minerals and probiotics. 
  6. ^ "About Us". Natural Products Foundation. Retrieved 2013-12-07. Natural products are represented by a wide array of consumer goods that continue to grow in popularity each year. These products include natural and organic foods, dietary supplements, pet foods, health and beauty products, "green" cleaning supplies and more. Generally, natural products are considered those formulated without artificial ingredients and that are minimally processed. 
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  40. ^ Kano S (2014). "Artemisinin-based combination therapies and their introduction in Japan". Kansenshogaku Zasshi 88 (3 Suppl 9-10): 18–25.  
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  43. ^ a b c Fernandes-Pedrosa MF, Félix-Silva J, Menezes YAS (2013). An Integrated View of the Molecular Recognition and Toxinology: From Analytical Procedures to Biomedical Applications (PDF). InTechOpen. pp. 23–72. 
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See also

Research is being carried out to understand and manipulate the biochemical pathways involved in natural product synthesis in plants. It is hoped this knowledge will enable medicinally useful phytochemicals such as alkaloids to be produced more efficiently and economically.[76]


Natural products chemistry is a distinct area of chemical research which was important in the Evans aldol reaction), as well as the discovery of completely new chemical reactions (e.g., the Woodward cis-hydroxylation, Sharpless epoxidation, and Suzuki–Miyaura cross-coupling reactions).


Research and teaching activities related to natural products fall into a number of different academic areas, including medicinal chemistry, pharmacognosy, ethnobotany, traditional medicine and ethnopharmacology. Other biological areas include chemical biology, chemical ecology, chemogenomics, and systems biology.

Research and teaching

Examination of dimerized and trimerized natural products has shown that an element of bilateral symmetry is often present. Bilateral symmetry refers to a molecule or system that contains a C2, Cs, or C2v point group identity. C2 symmetry tends to be much more abundant than other types of bilateral symmetry. This finding sheds light on how these compounds might be mechanistically created, as well as providing insight into the thermodynamic properties that make these compounds more favorable. Density functional theoretical (DFT), Hartree Fock, and semiempirical calculations also show some favorability for dimerization in natural products due to evolution of more energy per bond than the equivalent trimer or tetramer. This is proposed to be due to steric hindrance at the core of the molecule, as most natural products dimerize and trimerize in a head-to-head fashion rather than head-to-tail.[75]


[72][71].metabolism in cellular cofactor), an essential 12 (vitamin Bcobalamin targeted complex substances such as natural products synthesis). Early efforts in proof-by-synthesis Also, no natural product structure is considered fully affirmed by science until it has been produced by total synthesis (so-called [74][73] In general, the

Structural representation of cobalamin, an early natural product isolated and structurally characterized.[70] The variable R group can be a methyl or 5'-adenosyl group, or a cyanide or hydroxide anion. The "proof" by synthesis of vitamin B12 was accomplished in 1972 by the groups of R.B. Woodward[71] and A. Eschenmoser.[72]

Total synthesis

This strategy can have two advantages. Firstly, the intermediate may be more easily extracted, and in higher yield, than the ultimate desired product. An example of this is paclitaxel, which can be manufactured by extracting 10-deacetylbaccatin III from T. brevifolia needles, then carrying out a four-step synthesis. Secondly, the route designed between semisynthetic starting material and ultimate product may permit analogues of the final product to be synthesized. The newer generation semisynthetic penicillins are an illustration of the benefit of this approach.

The process of isolating a natural product from its source can be costly in terms of committed time and material expense, and it may challenge the availability of the relied upon natural resource (or have ecological consequences for the resource). For instance, it has been estimated that the semisynthesis or partial synthesis. With this approach, the related biosynthetic intermediate is harvested and then converted to the final product by conventional procedures of chemical synthesis.


Many natural products have very complex structures. The perceived complexity of a natural product is a qualitative matter, consisting of consideration of its molecular mass, the particular arrangements of substructures (functional groups, rings etc.) with respect to one another, the number and density of those functional groups, the stability of those groups and of the molecule as a whole, the number and type of stereochemical elements, the physical properties of the molecule and its intermediates (which bear on the ease of its handling and purification), all of these viewed in the context of the novelty of the structure and whether preceding related synthetic efforts have been successful (see below for details). Some natural products, especially those less complex, are easily and cost-effectively prepared via complete chemical synthesis from readily available, simpler chemical ingredients, a process referred to as total synthesis (especially when the process involves no steps mediated by biological agents). Not all natural products are amenable to total synthesis, cost-effective or otherwise. In particular, those most complex often are not. Many are accessible, but the required routes are simply too expensive to allow synthesis on any practical or industrial scale. However, in order to be available for further study, all natural products must yield to isolation and purification. This may suffice if isolation provides appropriate quantities of the natural product for the intended purpose (e.g. as a drug to alleviate disease). Drugs such as penicillin, morphine, and paclitaxel proved to be affordably acquired at needed commercial scales solely via isolation procedures (without any significant synthetic chemistry contributing). However, in other cases, needed agents are not available without synthetic chemistry manipulations.


Structure determination refers to methods applied to determine the chemical structure of an isolated, pure natural product, a process that involves an array of chemical and physical methods that have changed markedly over the history of natural products research; in earliest days, these focused on chemical transformation of unknown substances into known substances, and measurement of physical properties such as melting point and boiling point, and related methods for determining molecular weight. In the modern era, methods focus on mass spectrometry and nuclear magnetic resonance methods, often multidimensional, and, when feasible, small molecule crystallography. For instance, the chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in 1945, work for which she later received a Nobel Prize in Chemistry (1964).[68]

All natural products begin as mixtures with other compounds from the natural source, often very complex mixtures, from which the product of interest must be isolated and purified. The isolation of a natural product refers, depending on context, either to the isolation of sufficient quantities of pure chemical matter for chemical structure elucidation, derivitzation/degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but historically, often more), or to the isolation of "analytical quantities" of the substance of interest, where the focus is on identification and quantitation of the substance (e.g. in biological tissue or fluid), and where the quantity isolated depends on the analytical method applied (but is generally always sub-microgram in scale).[67] The ease with which the active agent can be isolated and purified depends on the structure, stability, and quantity of the natural product. The methods of isolation applied toward achieving these two distinct scales of product are likewise distinct, but generally involve extraction, precipitation, adsorptions, chromatography, and sometimes crystallizations. In both cases, the isolated substance is purified to chemical homogeneity, i.e. specific combined separation and analytical methods such as LC-MS methods are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—with the goal being repeated detection of only a single species present in the putative pure sample. Early isolation is almost inevitably followed by structure determination, especially if an important pharmacologic activity is associated with the purified natural product.

Penicillin G, the first of its class fungal antibiotic, first studied by Scottish microbiologist Alexander Fleming in the late 1920s, and made practical as a therapeutic via natural product isolation in the late 1930s by Ernst Boris Chain, Howard Florey, and others, these three named scientists sharing the 1945 Nobel Prize in Medicine for the work. Fleming recognized the antibacterial activity and clinical potential of "pen G", but was unable to purify or stabilize it.[66] Developments in chromatographic separations and freeze drying helped move progress forward in the production of commercial quantities of penicillin and other natural products.

Isolation and purification

A class of drugs widely used to lower cholesterol are the HMG-CoA reductase inhibitors, for example atorvastatin. These were developed from mevastatin, a polyketide produced by the fungus Penicillium citrinum.[64] Finally, a number natural product drugs are used to treat hypertension and congestive heart failure. These include the angiotensin-converting enzyme (ACE) inhbitior captopril. Captopril is based on the peptidic bradykinin potentiating factor (BPF) isolated from venom of the Brazilian arrowhead viper (Bothrops jararaca).[65]

Several natural product drugs target tubulin, which is a component of the cytoskeleton. These include the tubulin polymerization inhibitor colchicine isolated from the Colchicum autumnale (autumn crocus flowering plant), which is used to treat gout.[62] Colchicine is biosynthesized from the amino acids phenylalanine and tryptophan. Paclitaxel, in contrast, is a tubulin polymerization stabilizer and is used as a chemotherapeutic drug. Paclitaxel is based on the terpenoid natural product taxol, which is isolated from Taxus brevifolia (the pacific yew tree).[63]

A significant number of anti-infectives are based on natural products. The first antibiotic to be discovered, penicillin, was isolated from the mold Penicillium. Penicillin and related beta lactams work by inhibiting DD-transpeptidase enzyme that is required by bacteria to cross link peptidoglycan to form the cell wall.[61]

Some of the oldest natural product based drugs are analgesics. The bark of the willow tree has been known from antiquity to have pain relieving properties. This is due to presence of the natural product salicin which in turn may be hydrolyzed into salicylic acid. A synthetic derivative acetylsalicylic acid better known as aspirin is a widely used pain reliever. Its mechanism of action is inhibition of the cyclooxygenase (COX) enzyme.[58] Another notable example is opium is extracted from the latex from Papaver somniferous (a flowering poppy plant). The most potent narcotic component of opium is the alkaloid morphine which acts as an opioid receptor agonist.[59] A more recent example is the N-type calcium channel blocker ziconotide analgesic which is based on a cyclic peptide cone snail toxin (ω-conotoxin MVIIA) from the species Conus magus.[60]

A large number of currently prescribed drugs have been either directly derived from or inspired by natural products.[1] A few representative examples are listed below.

Modern natural product-derived drugs

Indigenous peoples and ancient civilizations experimented with various plant and animal parts to determine what effect they might have. Through trial and error, traditional healers or shamans found that some had healing power. These represented the first crude drugs and this knowledge was past down through the generations and systematized for example in traditional Chinese medicine and Ayurveda.[56] Many of these traditional medicines have real, beneficial effects and extracts of these crude drugs lead to the discovery of their active ingredients and eventually to the development of modern chemically pure drugs.[57]

Representative examples of drugs based on natural products

Traditional medicine and ethnopharmacology

Natural products sometimes have pharmacological or biological activity that can be of therapeutic benefit in treating diseases. As such, natural products are the active components of many traditional medicines.[51] Furthermore synthetic analogs of natural products with improved potency and safety can be prepared and therefore natural products are often used as starting points for drug discovery.[11][52][53] In fact, natural products are the inspiration for approximately one half of U.S. Food and Drug Administration-approved drugs.[54][55]

Medical uses

In addition to the terrestrial animals and amphibians described above, many marine animals have been examined for pharmacologically active natural products, with corals, sponges, tunicates, sea snails, and bryozoans yielding chemicals with interesting analgesic, antiviral, and anticancer activities.[44] Two examples developed for clinical use include ω-conotoxin (from the marine snail Conus magus)[45][46] and ecteinascidin 743 (from the tunicate Ecteinascidia turbinata).[47] The former, ω-conotoxin, is used to relieve severe and chronic pain,[46][48] while the latter, ecteinascidin 743 is used to treat metastatic soft tissue sarcoma.[49] Other natural products derived from marine animals and under investigation as possible therapies include the antitumour agents discodermolide (from the sponge Discodermia dissoluta),[50] eleutherobin (from the coral Erythropodium caribaeorum), and the bryostatins (from the bryozoan Bugula neritina).[50]

Because of these specific chemical-target interactions, venom constituents have proved important tools for studying receptors, ion channels, and enzymes. In some cases, they have also served as leads in the development of novel drugs. For example, teprotide, a peptide isolated from the venom of the Brazilian pit viper Bothrops jararaca, was a lead in the development of the antihypertensive agents cilazapril and captopril. Also, echistatin, a disintegrin from the venom of the saw-scaled viper Echis carinatus was a lead in the development of the antiplatelet drug tirofiban.[43]


The analgesic drug ω-conotoxin (ziconotide) is a natural product derived from the sea snail Conus magus


herbivory (feeding deterrents). Major classes of phytochemical include phenols, polyphenols, tannins, terpenes, and alkaloids.[38] Though the number of plants that have been extensively studied is relatively small, many pharmacologically active natural products have already been identified. Clinically useful examples include the anticancer agents paclitaxel and omacetaxine mepesuccinate (from Taxus brevifolia and Cephalotaxus harringtonii, respectively),[39] the antimalarial agent artemisinin (from Artemisia annua),[40] and the acetylcholinesterase inhibitor galantamine (from Galanthus spp.), used to treat Alzheimer's disease.[41] Other plant-derived drugs, used medicinally and/or recreationally include morphine, cocaine, quinine, tubocurarine, muscarine, and nicotine.[19]:Chapter 6

The opioid analgesic drug morphine is a natural product derived from the plant Papaver somniferum


Several anti-infective medications have been derived from ergometrine (from Claviceps spp.), which acts as a vasoconstrictor, and is used to prevent bleeding after childbirth.[19]:Chapter 6 Asperlicin (from Aspergillus alliaceus) is another example. Asperlicin is a novel antagonist of cholecystokinin, a neurotransmitter thought to be involved in panic attacks, and could potentially be used to treat anxiety.

The antibiotic penicillin is a natural product derived from the fungus Penicillium chrysogenum



Because many Archaea have adapted to life in extreme environments such as polar regions, hot springs, acidic springs, alkaline springs, salt lakes, and the high pressure of deep ocean water, they possess enzymes that are functional under quite unusual conditions. These enzymes are of potential use in the food, chemical, and pharmaceutical industries, where biotechnological processes frequently involve high temperatures, extremes of pH, high salt concentrations, and / or high pressure. Examples of enzymes identified to date include amylases, pullulanases, cyclodextrin glycosyltransferases, cellulases, xylanases, chitinases, proteases, alcohol dehydrogenase, and esterases.[35] Archaea represent a source of novel chemical compounds also, for example isoprenyl glycerol ethers 1 and 2 from Thermococcus S557 and Methanocaldococcus jannaschii, respectively.[36]


Although most of the drugs derived from bacteria are employed as anti-infectives, some have found use in other fields of medicine. Botulinum toxin (from Clostridium botulinum) and bleomycin (from Streptomyces verticillus) are two examples. Botulinum, the neurotoxin responsible for botulism, can be injected into specific muscles (such as those controlling the eyelid) to prevent muscle spasm.[29] Also, the glycopeptide bleomycin is used for the treatment of several cancers including Hodgkin's lymphoma, head and neck cancer, and testicular cancer.[30] Newer trends in the field include the metabolic profiling and isolation of natural products from novel bacterial species present in underexplored environments. Examples include symbionts or endophytes from tropical environments,[31] subterranean bacteria found deep underground via mining/drilling,[32][33] and marine bacteria.[34]

The serendipitous discovery and subsequent clinical success of streptomycin (derived from Streptomyces griseus), and the realization that bacteria, not just fungi, represent an important source of pharmacologically active natural products.[25] This, in turn, led to the development of an impressive arsenal of antibacterial and antifungal agents including amphotericin B, chloramphenicol, daptomycin and tetracycline (from Streptomyces spp.),[26] the polymyxins (from Paenibacillus polymyxa),[27] and the rifamycins (from Amycolatopsis rifamycinica).[28]

Botulinum toxin types A and B (Botox, Dysport, Xeomin, MyoBloc), used both medicinally and cosmetically, are natural products from the bacterium Clostridium botulinum



This is because many biologically active natural products are secondary metabolites often with complex chemical structures. This has an advantage in that they are novel compounds but this complexity also makes difficult the synthesis of such compounds; instead the compound may need to be extracted from its natural source – a slow, expensive and inefficient process. As a result, there is usually an advantage in designing simpler analogues.

  • produced by total synthesis, or
  • a starting point (precursor) for a semisynthetic compound, or
  • a framework that serves as the basis for a structurally different compound arrived at by total/semisynthesis.

On the other hand, some medicines are developed from the natural product lead originally obtained from the natural source. This means the lead may be:

Pharmacognosy provides the tools to identify, select and process natural products destined for medicinal use. Usually, the natural product compound has some form of biological activity and that compound is known as the active principle - such a structure can evolve to become a discovery "lead". In this and related ways, some current medicines are obtained directly from natural sources.

Natural products may be extracted from the plants and animals.[24] A crude (unfractionated) extract from any one of these sources will contain a range of structurally diverse and often novel chemical compounds. Chemical diversity in nature is based on biological diversity, so researchers travel around the world obtaining samples to analyze and evaluate in drug discovery screens or bioassays. This effort to search for natural products is known as bioprospecting.


One molecule of acetyl-CoA (the "starter unit") and several molecules malonyl-CoA (the "extender units") are condensed by fatty acid synthase to produce fatty acids.[19]:Chapter 3 Fatty acid are essential components of lipid bilayers that form cell membranes as well as fat energy stores in animals.

Through the process of glycolysis sugars are broken down into acetyl-CoA. In an ATP dependent enzymatically catalyzed reaction, acetyl-CoA is carboxylated to form malonyl-CoA. Acetyl-CoA and malonyl-CoA undergo a Claisen condensation with lose of carbon dioxide to form acetoacetyl-CoA. Additional condensation reactions produce successively higher molecular weight poly-β-keto chains which are then converted into other polyketides.[19]:Chapter 3 The polyketide class of natural products have diverse structures and functions and include prostaglandins and macrolide antibiotics.

Fatty acids and polyketides

Carbohydrate are the products of plant photosynthesis and animal gluconeogenesis. Photosynthesis produces initially 3-phosphoglyceraldehyde, a three carbon atom containing sugar (a triose).[19]:Chapter 8 This triose in turn may be converted into glucose (a six carbon atom containing sugar) or a variety of pentoses (five carbon atom containing sugars) through the Calvin cycle. In animals, the three carbon precursors lactate or glycerol can be converted into pyruvate which in turn can be converted into carbohydrates in the liver.

cell walls of bacteria and plants.


The biosynthetic pathways leading to the major classes of natural products are described below.[12][19]:Chapter 2

Biosynthesis of primary and secondary metabolites.[19]:Chapter 2


General structural classes of secondary metabolites include alkaloids, phenylpropanoids, polyketides, and terpenoids, [7] which are described in more detail in the biosynthesis section below.

[23], these secondary metabolites have no specific function, but having the machinery in place to produce these diverse chemical structures is important and a few secondary metabolites are therefore produced and selected for.immune system An alternative view is that, in analogy to the [22] Secondary metabolites have a broad range of functions. These include

Secondary in contrast to primary metabolites are dispensable and not absolutely required for survival. Furthermore secondary metabolites typically have a narrow species distribution.

Representative examples of each of the major classes of secondary metabolites

Secondary metabolites

First messengers are signaling molecules that control metabolism or cellular differentiation. These signaling molecules include hormones and growth factors in turn are composed of peptides, biogenic amines, steroid hormones, auxins, gibberellins etc. These first messengers interact with cellular receptors which are composed of proteins. Cellular receptors in turn activate second messengers are used to relay the extracellular message to intracellular targets. These signaling molecules include the primary metabolites cyclic nucleotides, diacyl glycerol etc.[20]

DNA and RNA which store and transmit genetic information are composed of nucleic acid primary metabolites.[17]

Primary metabolite enzymatic cofactors include members of the vitamin B family. Vitamin B1 as thiamine diphosphate is a coenzyme for pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and transketolase which are all involved in carbohydrate metabolism. Vitamin B2 (riboflavin) is a constituent of FMN and FAD which are necessary for many redox reactions. Vitamin B3 (nicotinic acid or niacin), synthesized from tryptophan is a component of the coenzymes NAD+ and NADP+ which in turn are required for electron transport in the Krebs cycle, oxidative phosphorylation, as well as many other redox reactions. Vitamin B5 (pantothenic acid) is a constituent of coenzyme A, a basic component of carbohydrate and amino acid metabolism as well as the biosynthesis of fatty acids and polyketides. Vitamin B6 (pyridoxol, pyridoxal, and pyridoxamine) as pyridoxal 5′-phosphate is a cofactor for many enzymes especially transaminases involve in amino acid metabolism. Vitamin B12 (cobalamins) contain a corrin ring similar in structure to porphyrin and is an essential coenzyme for the catabolism of fatty acids as well for the biosynthesis of methionine.[19]:Chapter 2

Primary metabolites that are involved with energy production include phospholipids), cell walls (e.g. peptidoglycan, chitin), and cytoskeletons (proteins).[18]

Primary metabolites as defined by Kossel are components of basic metabolic pathways that are required for life. They are associated with essential cellular functions such as nutrient assimilation, energy production, and growth/development. They have a wide species distribution that span many phyla and frequently more than one kingdom. Primary metabolites include carbohydrates, lipids, amino acids, and nucleic acids[14][15] which are the basic building blocks of life.[16]

Molecular building blocks of life

Primary metabolites

Natural products especially within the field of medicinal chemistry and pharmacognosy.[12]

Following signal transduction pathways, some secondary metabolites have useful medicinal properties.


Natural products may be classified according to their biological function, biosynthetic pathway, or source as described below.

The remainder of this article restricts itself to this more narrow definition. [7] and includes the likes of [12][4] The broadest definition of natural product is anything that is produced by life,



  • Classes 1
  • Function 2
    • Primary metabolites 2.1
    • Secondary metabolites 2.2
  • Biosynthesis 3
    • Carbohydrates 3.1
    • Fatty acids and polyketides 3.2
  • Sources 4
    • Prokaryotic 4.1
      • Bacteria 4.1.1
      • Archaea 4.1.2
    • Eukaryotic 4.2
      • Fungi 4.2.1
      • Plants 4.2.2
      • Animals 4.2.3
  • Medical uses 5
    • Traditional medicine and ethnopharmacology 5.1
    • Modern natural product-derived drugs 5.2
  • Isolation and purification 6
  • Synthesis 7
    • Semisynthesis 7.1
    • Total synthesis 7.2
    • Symmetry 7.3
  • Research and teaching 8
    • Chemistry 8.1
    • Biochemistry 8.2
  • See also 9
  • References 10
  • Further reading 11
  • Journals 12
  • External links 13

Natural products sometimes have pharmacological or biological activity that can be of therapeutic benefit in treating diseases. As such, natural products are the active components not only of most traditional medicines but also many modern medicines. Furthermore, because the structural diversity of natural products exceeds that readily achievable by chemical synthesis, and synthetic analogs can be prepared with improved potency and safety, natural products are often used as starting points for drug discovery. In fact, natural products are the inspiration for approximately one half of U.S. Food and Drug Administration-approved drugs.

[11] Within the field of


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